tbuckley/cabot-search huggingface dataset:
Infographic. Oxford consensus on primary cam morphology and femoroacetabular impingement syndrome—natural history of primary cam morphology to inform clinical practice and research priorities on conditions affecting the young person’s hip
Authors: H Paul Dijkstra, Sean Mc Auliffe, Clare L Ardern, Joanne L Kemp, Andrea Britt Mosler, Amy Price, Paul Blazey, Dawn Richards, Abdulaziz Farooq, Andreas Serner, Eugene McNally, Vasco Mascarenhas, Richard W Willy, Ivan Stankovic, Jason L Oke, Karim M Khan, Sion Glyn-Jones, Mike Clarke, Trisha Greenhalgh
Journal: British Journal of Sports Medicine (2023)

InfographicThis infographic illustrates the natural history of primary cam morphology (PCM) to inform the Oxford Consensus Study's seven prioritised research domains on conditions affecting the young person's hip. 1 2 We share 16 key messages for athletes, patients, clinicians and researchers:1.Among other possible risk factors (including genetics), playing a highload sport like football (soccer) or ice hockey while growing (during adolescence) is the key risk factor for developing PCM. 3 4 2.Many young athletes have asymptomatic PCM.However, at present, no one knows how many; clinicians and researchers have 'measured' PCM in different ways (often using alpha angles on imaging). 53. PCM seems more common in males.Research on PCM in females is sparse; no studies have yet investigated how PCM develops in female athletes. 54. Clinicians and researchers cannot predict who will develop PCM.Therefore, coaches cannot, with confidence, manipulate training to reduce a young athlete's risk of developing PCM. 5. Most athletes who have PCM thrive; they compete with 'happy hips' and never develop symptoms.6.Some athletes with PCM develop symptoms like hip-related pain.This is called 'femoroacetabular impingement (FAI) syndrome.' 6A few athletes with FAI syndrome might develop hip osteoarthritis (OA) in the future. 77. Clinicians and researchers cannot yet predict the 'at risk' athletes with PCM who might develop hip disease such as FAI syndrome or hip OA.However, size matters; large alpha angles are associated with a greater risk of developing hip OA. 8 8.The word 'syndrome' has a negative connotation to many patients.Most athletes with FAI syndrome do well when treated with a combination of education and progressive exercise rehabilitation.on July 16,
Are There Specific Cancer Stem Cell Markers?
Authors: Linxiang Lan, Axel Behrens
Journal: Cancer Research (2023)

Abstract The cancer stem cell (CSC) model states that heterogeneous tumor cell populations are organized in a hierarchical manner, with a small population of CSCs at the apex. These CSCs are capable of self-renewal and giving rise to other cancer cell populations, conceptually analogous to the function of normal adult stem cells present in almost all organs. However, there has been significant controversy regarding the existence and identification of CSCs. We argue that technical differences in experimentation and CSC assays, CSC niche-dependency and plasticity, and CSC heterogeneity itself may explain some of the differences observed.
The impact of right atrial pressure on outcomes in patients undergoing TIPS, an ALTA group study
Authors: Shoma Bommena, Nadim Mahmud, Justin R. Boike, Bartley G. Thornburg, Kanti P. Kolli, Jennifer C. Lai, Margarita German, Giuseppe Morelli, Erin Spengler, Adnan Said, Archita P. Desai, Shilpa Junna, Sonali Paul, Catherine Frenette, Elizabeth C. Verna, Aparna Goel, Dyanna Gregory, Cynthia Padilla, Lisa B. VanWagner, Michael B. Fallon
Journal: Hepatology (2023)

Background and Aims: Single-center studies in patients undergoing TIPS suggest that elevated right atrial pressure (RAP) may influence survival. We assessed the impact of pre-TIPS RAP on outcomes using the Advancing Liver Therapeutic Approaches (ALTA) database. Approach and Results: Total 883 patients in ALTA multicenter TIPS database from 2010 to 2015 from 9 centers with measured pre-TIPS RAP were included. Primary outcome was mortality. Secondary outcomes were 48-hour post-TIPS complications, post-TIPS portal hypertension complications, and post-TIPS inpatient admission for heart failure. Adjusted Cox Proportional hazards and competing risk model with liver transplant as a competing risk were used to assess RAP association with mortality. Restricted cubic splines were used to model nonlinear relationship. Logistic regression was used to assess RAP association with secondary outcomes. Pre-TIPS RAP was independently associated with overall mortality (subdistribution HR: 1.04 per mm Hg, 95% CI, 1.01, 1.08, p =0.009) and composite 48-hour complications. RAP was a predictor of TIPS dysfunction with increased odds of post-90-day paracentesis in outpatient TIPS, hospital admissions for renal dysfunction, and heart failure. Pre-TIPS RAP was positively associated with model for end-stage liver disease, body mass index, Native American and Black race, and lower platelets. Conclusions: Pre-TIPS RAP is an independent risk factor for overall mortality after TIPS insertion. Higher pre-TIPS RAP increased the odds of early complications and overall portal hypertensive complications as potential mechanisms for the mortality impact.
Multicentered study of patient outcomes after declined for early liver transplantation in severe alcohol-associated hepatitis
Authors: Christine C. Hsu, Jennifer L. Dodge, Ethan Weinberg, Gene Im, Jimin Ko, William Davis, Stephanie Rutledge, Matthew Dukewich, Mohamed Shoreibah, Mahmoud Aryan, Aidan Vosooghi, Michael Lucey, John Rice, Norah A. Terrault, Brian P. Lee
Journal: Hepatology (2023)

Early liver transplantation for alcohol-associated hepatitis is controversial in part because patients may recover, and obviate the need for liver transplantation.
Targeting Microglial Metabolic Rewiring Synergizes with Immune-Checkpoint Blockade Therapy for Glioblastoma
Authors: Zengpanpan Ye, Xiaolin Ai, Kailin Yang, Zhengnan Yang, Fan Fei, Xiaoling Liao, Zhixin Qiu, Ryan C. Gimple, Huairui Yuan, Hao Huang, Yanqiu Gong, Chaoxin Xiao, Jing Yue, Liang Huang, Olivier Saulnier, Wei Wang, Peidong Zhang, Lunzhi Dai, Xin Wang, Xiuxing Wang, Young Ha Ahn, Chao You, Jianguo Xu, Xiaoxiao Wan, Michael D. Taylor, Linjie Zhao, Jeremy N. Rich, Shengtao Zhou
Journal: Cancer Discovery (2023)

Glioblastoma (GBM) constitutes the most lethal primary brain tumor for which immunotherapy has provided limited benefit. The unique brain immune landscape is reflected in a complex tumor immune microenvironment (TIME) in GBM. Here, single-cell sequencing of the GBM TIME revealed that microglia were under severe oxidative stress, which induced nuclear receptor subfamily 4 group A member 2 (NR4A2)-dependent transcriptional activity in microglia. Heterozygous Nr4a2 (Nr4a2+/-) or CX3CR1+ myeloid cell-specific Nr4a2 (Nr4a2fl/flCx3cr1Cre) genetic targeting reshaped microglia plasticity in vivo by reducing alternatively activated microglia and enhancing antigen presentation capacity for CD8+ T cells in GBM. In microglia, NR4A2 activated squalene monooxygenase (SQLE) to dysregulate cholesterol homeostasis. Pharmacologic NR4A2 inhibition attenuated the protumorigenic TIME, and targeting the NR4A2 or SQLE enhanced the therapeutic efficacy of immune-checkpoint blockade in vivo. Collectively, oxidative stress promotes tumor growth through NR4A2-SQLE activity in microglia, informing novel immune therapy paradigms in brain cancer. Metabolic reprogramming of microglia in GBM informs synergistic vulnerabilities for immune-checkpoint blockade therapy in this immunologically cold brain tumor. This article is highlighted in the In This Issue feature, p. 799.
Granzyme K contributes to endothelial microvascular damage and leakage during skin inflammation
Authors: Christopher T Turner, Matthew R Zeglinski, Wendy Boivin, Hongyan Zhao, Megan A Pawluk, Katlyn C Richardson, Arundhasa Chandrabalan, Phillip Bird, Rithwik Ramachandran, Roma Sehmi, Hermenio Lima, Gail Gauvreau, David J Granville
Journal: British Journal of Dermatology (2022)

Abstract Background Granzyme K (GzmK) is a serine protease with minimal presence in healthy tissues while abundant in inflamed tissues. Initially thought to play an exclusive role in immune-mediated cell death, extracellular GzmK can also promote inflammation. Objectives To evaluate the role of GzmK in the pathogenesis of atopic dermatitis (AD), the most common inflammatory skin disease. Methods A panel of human AD and control samples was analysed to determine if GzmK is elevated. Next, to determine a pathological role for GzmK in AD-like skin inflammation, oxazolone-induced dermatitis was induced in GzmK−/− and wild-type (WT) mice. Results In human lesional AD samples, there was an increase in the number of GzmK+ cells compared with healthy controls. GzmK−/− mice exhibited reduced overall disease severity characterized by reductions in scaling, erosions and erythema. Surprisingly, the presence of GzmK did not notably increase the overall pro-inflammatory response or epidermal barrier permeability in WT mice; rather, GzmK impaired angiogenesis, increased microvascular damage and microhaemorrhage. Mechanistically, GzmK contributed to vessel damage through cleavage of syndecan-1, a key structural component of the glycocalyx, which coats the luminal surface of vascular endothelia. Conclusions GzmK may provide a potential therapeutic target for skin conditions associated with persistent inflammation, vasculitis and pathological angiogenesis.
Gestational age at birth and cognitive outcomes in adolescence: population based full sibling cohort study
Authors: Anders Husby, Jan Wohlfahrt, Mads Melbye
Journal: BMJ (2023)

To investigate the association between gestational age at birth and cognitive outcomes in adolescence.Nationwide population based full sibling cohort study.Denmark.1.2 million children born between 1 January 1986 and 31 December 2003, of whom 792 724 had one or more full siblings born in the same period.Scores in written language (Danish) and mathematics examinations as graded by masked assessors at the end of compulsory schooling (ninth grade, ages 15-16 years), in addition to intelligence test score at military conscription (predominantly at age 18 years) for a nested sub-cohort of male adolescents. School grades were standardised as z scores according to year of examination, and intelligence test scores were standardised as z scores according to year of birth.Among 792 724 full siblings in the cohort, 44 322 (5.6%) were born before 37+0 weeks of gestation. After adjusting for multiple confounders (sex, birth weight, malformations, parental age at birth, parental educational level, and number of older siblings) and shared family factors between siblings, only children born at <34 gestational weeks showed reduced mean grades in written language (z score difference -0.10 (95% confidence interval -0.20 to -0.01) for ≤27 gestational weeks) and mathematics (-0.05 (-0.08 to -0.01) for 32-33 gestational weeks, -0.13 (-0.17 to -0.09) for 28-31 gestational weeks, and -0.23 (-0.32 to -0.15) for ≤27 gestational weeks), compared with children born at 40 gestational weeks. In a nested sub-cohort of full brothers with intelligence test scores, those born at 32-33, 28-31, and ≤27 gestational weeks showed a reduction in IQ points of 2.4 (95% confidence interval 1.1 to 3.6), 3.8 (2.3 to 5.3), and 4.2 (0.8 to 7.5), respectively, whereas children born at 34-39 gestational weeks showed a reduction in intelligence of <1 IQ point, compared with children born at 40 gestational weeks.Cognitive outcomes in adolescence did not differ between those born at 34-39 gestational weeks and those born at 40 gestational weeks, whereas those with a gestational age of <34 weeks showed substantial deficits in multiple cognitive domains.
Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction
Authors: Kazuo Miyazawa, Kaoru Ito, Masamichi Ito, Zhaonan Zou, Masayuki Kubota, Seitaro Nomura, Hiroshi Matsunaga, Satoshi Koyama, Hirotaka Ieki, Masato Akiyama, Yoshinao Koike, Ryo Kurosawa, Hiroki Yoshida, Kouichi Ozaki, Yoshihiro Onouchi, Koichi Matsuda, Yoshinori Murakami, Yoichiro Kamatani, Atsushi Takahashi, Koichi Matsuda, Yoshinori Murakami, Hiroyuki Aburatani, Michiaki Kubo, Yukihide Momozawa, Chikashi Terao, Shinya Oki, Hiroshi Akazawa, Yoichiro Kamatani, Issei Komuro
Journal: Nature Genetics (2023)

Abstract Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9,826 cases among 150,272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of &gt;1 million individuals, including 77,690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications.
Risk of Surgical Mitral Valve Repair for Primary Mitral Regurgitation
Authors: Vinay Badhwar, Joanna Chikwe, A. Marc Gillinov, Sreek Vemulapalli, Patrick T. O’Gara, J. Hunter Mehaffey, Moritz Wyler von Ballmoos, Michael E. Bowdish, Elizabeth L. Gray, Sean M. O’Brien, Vinod H. Thourani, David M. Shahian, Robert H. Habib
Journal: Journal of the American College of Cardiology (2023)
Endogenous Electric Field‐Coupled PD@BP Biomimetic Periosteum Promotes Bone Regeneration through Sensory Nerve via Fanconi Anemia Signaling Pathway
Authors: Yanlin Su, Lian Zeng, Rongli Deng, Bing Ye, Shuo Tang, Zekang Xiong, Tingfang Sun, Qiuyue Ding, Weijie Su, Xirui Jing, Qing Gao, Xiumei Wang, Zhiye Qiu, Kaifang Chen, Daping Quan, Xiaodong Guo
Journal: Advanced Healthcare Materials (2023)

Abstract To treat bone defects, repairing the nerve‐rich periosteum is critical for repairing the local electric field. In this study, an endogenous electric field is coupled with 2D black phosphorus electroactive periosteum to explore its role in promoting bone regeneration through nerves. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) are used to characterize the electrically active biomimetic periosteum. Here, the in vitro effects exerted by the electrically active periosteum on the transformation of Schwann cells into the repair phenotype, axon initial segment (AIS) and dense core vesicle (DCV) of sensory neurons, and bone marrow mesenchymal stem cells are assessed using SEM, immunofluorescence, RNA‐sequencing, and calcium ion probes. The electrically active periosteum stimulates Schwann cells into a neuroprotective phenotype via the Fanconi anemia pathway, enhances the AIS effect of sensory neurons, regulates DCV transport, and releases neurotransmitters, promoting the osteogenic transformation of bone marrow mesenchymal stem cells. Microcomputed tomography and other in vivo techniques are used to study the effects of the electrically active periosteum on bone regeneration. The results show that the electrically active periosteum promotes nerve‐induced osteogenic repair, providing a potential clinical strategy for bone regeneration.
Survival update of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma in the OpACIN and OpACIN-neo trials
Authors: J.M. Versluis, A.M. Menzies, K. Sikorska, E.A. Rozeman, R.P.M. Saw, W.J. van Houdt, H. Eriksson, W.M.C. Klop, S. Ch’ng, J.V. van Thienen, H. Mallo, M. Gonzalez, A. Torres Acosta, L.G. Grijpink-Ongering, A. van der Wal, A. Bruining, B.A. van de Wiel, R.A. Scolyer, J.B.A.G. Haanen, T.N. Schumacher, A.C.J. van Akkooi, G.V. Long, C.U. Blank
Journal: Annals of Oncology (2023)
Efficacy of Local Treatment in Lymph Node Metastasis from Hepatocellular Carcinoma
Authors: Byung min Lee, Jin-Young Choi, Jinsil Seong
Journal: Liver Cancer (2023)

We aimed to investigate the significance of lymph node metastasis from hepatocellular carcinoma and the efficacy of local treatment.We included patients diagnosed hepatocellular carcinoma with lymph node metastasis. The pattern of lymph node metastasis was evaluated based on imaging examinations and stratified by three locations: regional (group A), beyond regional intra-abdomen (group B), and extra-abdomen (group C) lymph node metastasis.Among 14,474 patients, 852 (5.8%) were identified as having lymph node metastasis. Regarding the location of presentation, group A showed the highest incidence, followed by groups B and C. The 1-year overall survival of patients was 31.7%. The survival significantly differed according to the location of lymph node metastasis. The 1-year overall survival rates were 39.8%, 25.5%, and 22.2% in groups A, B, and C, respectively. All patients underwent systemic treatment, with others receiving additional local treatment. Local treatment yielded superior overall survival compared with no local treatment. After propensity score matching, local treatment was associated with improved survival. Additionally, patients were stratified based on disease status at the time of diagnosis of lymph node metastasis: lymph node alone and combined extra-nodal metastasis. The survival benefits of local treatment were observed in both groups.Our findings demonstrated the clinical significance of lymph node metastasis from hepatocellular carcinoma, which was well discriminated according to location, favoring regional metastasis. In patients with hepatocellular carcinoma presenting lymph node metastasis, active application of local treatment for lymph node metastasis can improve oncologic outcomes.
How I approach bleeding in hospitalized patients
Authors: Bethany Samuelson Bannow, Barbara A. Konkle
Journal: Blood (2023)

Excessive bleeding is relatively common in adult inpatients, whether as the primary reason for admission or as a development during the hospital stay. Common causes include structural issues, medication effects, and systemic illnesses; occasionally, unexpected bleeding can develop as a result of an undiagnosed or newly acquired bleeding disorder. The first step in caring for the inpatient who is bleeding is to determine whether the bleeding symptom is truly new or whether the patient has a history of abnormal bleeding. Patients with a history of abnormal bleeding may warrant evaluation for inherited bleeding disorders, such as platelet function disorders, von Willebrand disease, hemophilia, or rare factor deficiencies. Patients with no history of bleeding, for whom other causes, such as liver dysfunction, medication effect, disseminated intravascular coagulation, or certain vitamin deficiencies have been ruled out may require evaluation for acquired coagulopathies, such as acquired hemophilia or acquired von Willebrand disease. Here, we present 3 cases to discuss the diagnosis and management of the 2 most common acquired bleeding disorders as well as a patient with a congenital bleeding disorder with a historical diagnosis.
NIH Pilots Telehealth Program for COVID-19
Authors: Howard D. Larkin
Journal: JAMA (2023)

A treatment that may moderately slow mild cognitive decline and reduce amyloid-β plaques in patients with early Alzheimer disease gained accelerated approval from the US Food and Drug Administration (FDA).Lecanemab-irmb, marketed as Leqembi by Eisai and Biogen, is indicated for patients with mild cognitive impairment or mild dementia due to Alzheimer disease.In a clinical trial involving 1795 patients, those receiving lecanemab showed slower cognitive decline than those receiving a placebo after 18 months of treatment.In a substudy of 698 patients, those receiving lecanemab also showed greater reductions in amyloid-β plaques, which was the basis for the FDA's accelerated approval.Lecanemab's label warnings include the possibility of amyloid-related imaging abnormalities, such as edema or effusions, and infusion-related reactions.It is the second monoclonal antibody approved for Alzheimer disease.Continued approval may be subject to verification of clinical effect in a confirmatory trial.
Patients With Mild COVID-19 at Risk of Some Post–COVID-19 Condition Symptoms
Authors: Howard D. Larkin
Journal: JAMA (2023)

Patients who were diagnosed with mild COVID-19 were up to 4.6 times more likely than uninfected patients to have some symptoms associated with post–COVID-19 condition (PCC) for 6 to 12 months, according to a study in The BMJ.
Lecanemab Gains FDA Approval for Early Alzheimer Disease
Authors: Howard D. Larkin
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Gene Edited Tumor Cells Kill and Prevent Cancer in Mice
Authors: Howard D. Larkin
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal